Preterm delivery (PTD) and low birth weight (LBW) complicate over 12% of deliveries annually in the U.S. About two-thirds of all infant deaths occur among neonates that are born less than 2500 gms. Studies find that women who have elevated scores on depression screening scales are at increased risk for delivering a preterm or low birth weight infant. Similarly controlled studies of women using antidepressant agents show an increased risk for delivering an infant preterm. Despite this literature, no epidemiological study has examined the effect of a depressive disorder or its pharmacological treatment on adverse perinatal outcomes. We propose to conduct a prospective cohort study to determine whether a depressive disorder increases the risk of preterm delivery (<37 weeks), early preterm delivery (<=34 weeks), low birth weight (<2500 gms) or intrauterine growth retardation (IUGR). We will: (1) use structured interviewing to diagnose depressive disorders during pregnancy rather than relying on depression screening measures; (2) determine the point at which the woman developed the disorder by conducting prospective, longitudinal assessments of psychiatric illness during pregnancy; (3) recruit an ethnically and economically broad based cohort to explore associations among depression and demographic factors; (4) collect information on antidepressant and other medication use to determine whether the illness, or its pharmacological treatment accounts for the effects on birth weight and gestational duration. The study will have at least 85% power to detect associations between depressive illnesses in each trimester of pregnancy and PTD, EPTD, LBW and IUGR. To accomplish this, we will enroll 680 women with current depression, 680 women with a history of depression in the past 5 years, but not currently depressed, and 2040 non-depressed controls. An extensive psychiatric and perinatal risk factor interview will take place at enrollment. Telephone follow up at 22 and 32 weeks gestation, and 3 months postpartum will reevaluate diagnosis, severity of depression, antidepressant use and other risk factors. The independent effect of illness and antidepressants on these outcomes will be evaluated and we will examine whether specific symptoms of depression contribute to poor perinatal outcomes. This study has critical implications. If depression increases the risk of preterm delivery, early preterm delivery, low birth weight or IUGR, clinicians will need to implement even more rigorous efforts to treat it. Further, if we determine antidepressants increase the risk of adverse perinatal outcomes, treatment with psychotherapy rather than antidepressants should be considered when recommending therapeutic options. [unreadable] [unreadable]